We describe an 8-year-old girl who sustained multiple compound fractures in an accident involving agricultural equipment. She developed Scedosporium prolificans osteomyelitis of the pelvis, septic arthritis of the hip, and myositis of adjacent muscles. The infection progressed, despite extensive surgical debridement and joint washouts with 0.2% polyhexamethylene biguanide; antifungal therapy with caspofungin, terbinafine, and voriconazole; and adjunctive therapy with interferon-gamma. Gradual resolution was achieved after the addition of a novel agent, hexadecylphospocholine (miltefosine), and the continuation of terbinafine and voriconazole. This is the first report of the use of miltefosine as an antifungal agent in the management of severe infection with S. prolificans.